The supply of morphine and morphine-derived products in medicine depends on the isolation of major constituents of the opium poppy such as morphine 1, codeine 2 and thebaine 3, the structures of which are shown below.

The alkaloids are then converted by semi-synthesis to other medicinally useful agents such as hydrocodone 4, oxycodone 5, naltrexone 6, and naloxone 7.
Because of the commercial importance of these products, many attempts have been made to find an efficient method for their production. For example, United States Patent Application 2006/0167258 discloses a process for the manufacture of dihydrothebaine, dihydrocodeinone enol acetate, hydrocodone, and analogs thereof by reacting dihydrocodeine or analogs thereof with benzophenone in the presence of potassium tert-alkylate in a hydrocarbon solvent to generate a reaction mixture containing an enolate of the corresponding ketone, followed by addition of the reaction mixture to the electrophilic agent and isolation of the product. United States Patent No. 2006/0074239 discloses a method for the catalytic conversion of codeine, morphine or analogs thereof into hydrocodone, hydromorphone or analogs thereof utilizing a transition metal complex of a tertiary phosphine halide as catalyst. United States Patent Application 2003/0045720 discloses a method for the production of hydromorphone and hydrocodone from an alkaloid that comprises mixing the narcotic alkaloid with an acid in the presence of a catalyst wherein the method is carried out in the substantial absence of hydrogen gas. U.S. Pat. No. 5,571,685 discloses a method for the production of hydrocodone from neopinone or codeinone involving a morphinone reductase enzyme. Methods for the production of other derivatives can be found, for example, in U.S. Pat. Nos. 6,235,906; 6,291,675; 6,864,370 and 7,129,248.
Thebaine is a particularly useful opiate alkaloid that can be converted into a variety of compounds such as hydrocodone, oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, buprenorphine and etorphine. The use of thebaine as a precursor alkaloid has been limited by the fact that it is a minor constituent of the latex obtained from the opium poppy. However, with the advent of genetically engineered plants, the content of thebaine in the latex may exceed 30%. Thebaine can be isolated as a major component from genetically altered plants introduced by Tasmanian Alkaloids and described in U.S. Pat. No. 6,067,749.
Since thebaine can now be isolated in significant amounts, it could be an ideal starting material for the semi-synthetic opioid derivatives, such as hydrocodone and oxycodone. However, conversion of thebaine to the derivatives using current methods results in the production of undesirable intermediates. Recent recommendations from the ICH (International Conference on Harmonisation) recommend that the amount of α, β-unsaturated ketone containing compounds should be limited in pharmaceutical preparations (ICH Safety Guidelines, ICH S2A, 1995: ICH S2B, 1997). Thus, there has been an unmet need for new methods for the synthesis of morphine derivatives that avoid the production of such intermediates/impurities and that are cost efficient.